2020
An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint
Ramanan D, Sefik E, Galván-Peña S, Wu M, Yang L, Yang Z, Kostic A, Golovkina T, Kasper D, Mathis D, Benoist C. An Immunologic Mode of Multigenerational Transmission Governs a Gut Treg Setpoint. Cell 2020, 181: 1276-1290.e13. PMID: 32402238, PMCID: PMC7393667, DOI: 10.1016/j.cell.2020.04.030.Peer-Reviewed Original ResearchConceptsDouble-negative feedback loopTreg proportionImmunological modeGut immune responseGut commensalsControlling gut inflammationSpecies levelInbred mouse strainsMulti-generational transmissionTreg-dependent mannerCellular perturbationsRegulatory T cellsDisease susceptibilityNon-epigeneticMaternal transmissionInflammatory disease susceptibilityNon-geneticGut inflammationT cellsGenetic tuningMouse strainsImmune responseMultiple generationsImmune systemFeedback loopEnteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity
Jarret A, Jackson R, Duizer C, Healy ME, Zhao J, Rone JM, Bielecki P, Sefik E, Roulis M, Rice T, Sivanathan KN, Zhou T, Solis AG, Honcharova-Biletska H, Vélez K, Hartner S, Low JS, Qu R, de Zoete MR, Palm NW, Ring AM, Weber A, Moor AE, Kluger Y, Nowarski R, Flavell RA. Enteric Nervous System-Derived IL-18 Orchestrates Mucosal Barrier Immunity. Cell 2020, 180: 50-63.e12. PMID: 31923399, PMCID: PMC7339937, DOI: 10.1016/j.cell.2019.12.016.Peer-Reviewed Original ResearchConceptsEnteric nervous systemSingle-cell sequencingMucosal barrier immunitySingle-molecule fluorescenceIL-18Non-redundant roleSitu mRNA hybridization studiesEpithelial cellsUnbiased RNA sequencingRNA sequencingProtein responseBarrier immunityNervous systemConfocal microscopyCytokine IL-18Hybridization studiesInvasive bacterial infectionsSalmonella typhimurium infectionSequencingProfound consequencesIntestinal neuronsEnteric neuronsIntestinal immunityMucosal barrierTyphimurium infection
2017
Mining the Human Gut Microbiota for Immunomodulatory Organisms
Geva-Zatorsky N, Sefik E, Kua L, Pasman L, Tan T, Ortiz-Lopez A, Yanortsang T, Yang L, Jupp R, Mathis D, Benoist C, Kasper D. Mining the Human Gut Microbiota for Immunomodulatory Organisms. Cell 2017, 168: 928-943.e11. PMID: 28215708, PMCID: PMC7774263, DOI: 10.1016/j.cell.2017.01.022.Peer-Reviewed Original ResearchConceptsGut microbiotaHuman gut microbesHuman gut microbiotaIndividual bacterial speciesGut microbesMicrobial phylogenyHuman gutDiverse microbesEpigenetic systemsMicrobial diversityBacterial speciesMicrobiota's abilityMicrobesMicrobiotaMonocolonized miceGutImmunological adaptationsHostImmune systemPhylogenyImmune parametersPhylogeneticallyImmunomodulatory effectsSpeciesDiversity
2016
Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice
Tan T, Sefik E, Geva-Zatorsky N, Kua L, Naskar D, Teng F, Pasman L, Ortiz-Lopez A, Jupp R, Wu H, Kasper D, Benoist C, Mathis D. Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e8141-e8150. PMID: 27911839, PMCID: PMC5167147, DOI: 10.1073/pnas.1617460113.Peer-Reviewed Original ResearchConceptsIntestinal Th17 cellsB. adolescentisTh17 cell accumulationTh17 cellsHuman gutBifidobacterium strainsBifidobacterium adolescentisBacterial speciesTranscriptional programsIdentified speciesSymbiont bacteriaCell accumulationProbiotic preparationGut epitheliumInduce Th17 cellsMurine intestineK/BxN mouse modelFunctional microbesInoculation of miceFilamentous bacteriaMicrobesAttending inflammationBacteriaGutAutoimmune arthritis
2015
Control of peripheral tolerance by regulatory T cell–intrinsic Notch signaling
Charbonnier L, Wang S, Georgiev P, Sefik E, Chatila T. Control of peripheral tolerance by regulatory T cell–intrinsic Notch signaling. Nature Immunology 2015, 16: 1162-1173. PMID: 26437242, PMCID: PMC4618075, DOI: 10.1038/ni.3288.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsEpigenesis, GeneticFemaleForkhead Transcription FactorsGraft vs Host DiseaseMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, TransgenicMutationPeripheral ToleranceRapamycin-Insensitive Companion of mTOR ProteinReceptor, Notch1Recombinant Fusion ProteinsSignal TransductionTh1 CellsT-Lymphocytes, RegulatoryTranscriptomeIndividual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells
Sefik E, Geva-Zatorsky N, Oh S, Konnikova L, Zemmour D, McGuire AM, Burzyn D, Ortiz-Lopez A, Lobera M, Yang J, Ghosh S, Earl A, Snapper SB, Jupp R, Kasper D, Mathis D, Benoist C. Individual intestinal symbionts induce a distinct population of RORγ+ regulatory T cells. Science 2015, 349: 993-997. PMID: 26272906, PMCID: PMC4700932, DOI: 10.1126/science.aaa9420.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBacteriaBacteroidetesColitis, UlcerativeColonForkhead Transcription FactorsHomeostasisHumansImmunity, MucosalIntestinal MucosaMice, Inbred C57BLMicrobiotaNuclear Receptor Subfamily 1, Group F, Member 3SymbiosisTh17 CellsT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryTranscription, GeneticTranscriptomeConceptsRegulatory T cellsImmuno-inflammatory responseT helper 17 (Th17) cell differentiationTranscription factor Foxp3Important effector moleculeRegulatory cellsHuman gut microbiotaFactor Foxp3T cellsRelated cell typesGut microbiotaMouse colonRORγSymbiotic membersIntestinal symbiontsFoxp3Tissue homeostasisEffector moleculesCell differentiationCell typesDistinct populationsCellsDifferent outcomesInflammation
2014
Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut
Morton A, Sefik E, Upadhyay R, Weissleder R, Benoist C, Mathis D. Endoscopic photoconversion reveals unexpectedly broad leukocyte trafficking to and from the gut. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 6696-6701. PMID: 24753589, PMCID: PMC4020091, DOI: 10.1073/pnas.1405634111.Peer-Reviewed Original ResearchConceptsIntestinal microbiotaKaede transgenic miceFluorescent reportersIntestinal leukocytesFilamentous bacteriaGutMyeloid populationsK/BxN miceTh17 cellsEndoscopic approachImmune cellsLeukocyte subsetsAutoinflammatory diseasesImmune homeostasisDescending colonTransgenic miceLeukocyte movementLeukocytesMounting evidenceCellsMiceMicrobiotaTraffickingBacteriaTreg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses
Joller N, Lozano E, Burkett PR, Patel B, Xiao S, Zhu C, Xia J, Tan TG, Sefik E, Yajnik V, Sharpe AH, Quintana FJ, Mathis D, Benoist C, Hafler DA, Kuchroo VK. Treg Cells Expressing the Coinhibitory Molecule TIGIT Selectively Inhibit Proinflammatory Th1 and Th17 Cell Responses. Immunity 2014, 40: 569-581. PMID: 24745333, PMCID: PMC4070748, DOI: 10.1016/j.immuni.2014.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCells, CulturedCytokinesEosinophilsFibrinogenForkhead Transcription FactorsGene Expression ProfilingGene Expression RegulationImmunosuppression TherapyLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicReceptors, ImmunologicRespiratory HypersensitivityTh1-Th2 BalanceT-Lymphocyte SubsetsT-Lymphocytes, RegulatoryConceptsTreg cell subsetsTh2 cell responsesTreg cellsCell subsetsCell responsesProinflammatory T helper 1T effector cell proliferationTreg cell-mediated suppressionFibrinogen-like protein 2Allergic airway inflammationT regulatory (Treg) cellsTh2 cytokine productionSuppression of Th1T helper 1Effector cell proliferationTreg signature genesProinflammatory Th1TIGIT expressionAirway inflammationTh17 cellsRegulatory cellsHelper 1Cytokine productionT cellsImmune response
2013
A Special Population of Regulatory T Cells Potentiates Muscle Repair
Burzyn D, Kuswanto W, Kolodin D, Shadrach J, Cerletti M, Jang Y, Sefik E, Tan T, Wagers A, Benoist C, Mathis D. A Special Population of Regulatory T Cells Potentiates Muscle Repair. Cell 2013, 155: 1282-1295. PMID: 24315098, PMCID: PMC3894749, DOI: 10.1016/j.cell.2013.10.054.Peer-Reviewed Original ResearchConceptsTreg cellsMuscle repairDepletion of Treg cellsPopulation of Treg cellsSuppressors of immune responsesMuscle repair in vivoMyeloid lineage cellsGrowth factor amphiregulinSatellite cells in vitroImpaired muscle repairCells in vitroGenetically dystrophic miceProinflammatory infiltratesSkeletal muscle of miceMuscle of miceTreg activityTreg populationDystrophic miceImmune responseMuscular dystrophyTherapeutic opportunitiesNonimmunologic processesTregsWound repairMuscle damage
2011
Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice
Kriegel MA, Sefik E, Hill JA, Wu HJ, Benoist C, Mathis D. Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 2011, 108: 11548-11553. PMID: 21709219, PMCID: PMC3136249, DOI: 10.1073/pnas.1108924108.Peer-Reviewed Original ResearchConceptsDiabetes protectionSFB colonizationSmall intestinal lamina propriaSystemic lymphoid tissuesExperimental autoimmune encephalomyelitisNonobese diabetic (NOD) miceT cell compartmentImmune system alterationsType 1 diabetesDifferent Th subsetsSegmented filamentous bacteriaHost physiological functionsNOD miceAutoimmune encephalomyelitisInflammatory arthritisTh17 cellsTh subsetsAutoimmune responseDiabetic miceLymphoid tissueSI-LPSpontaneous modelT cellsLamina propriaMouse model
2010
Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival
Hand TW, Cui W, Jung YW, Sefik E, Joshi NS, Chandele A, Liu Y, Kaech SM. Differential effects of STAT5 and PI3K/AKT signaling on effector and memory CD8 T-cell survival. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 16601-16606. PMID: 20823247, PMCID: PMC2944719, DOI: 10.1073/pnas.1003457107.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD8-Positive T-LymphocytesCell SurvivalDown-RegulationImmunologic MemoryInterleukin-15Lectins, C-TypeLymphocytic choriomeningitis virusMiceMice, Inbred C57BLMice, Mutant StrainsMice, TransgenicPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, CytokineReceptors, ImmunologicSignal TransductionSTAT5 Transcription FactorConceptsCD8 T cell survivalT cell survivalPI3K/AktIL-15IL-7IL-15 receptor expressionAntiviral CD8 T cellsBCL2 expressionCD8 T cellsMemory precursor cellsProtective memory cellsAkt activationJAK/STAT5Effector cell deathEffector cellsHomeostatic proliferationReceptor expressionT cellsConstitutive Akt activationCell growth pathwaysConstitutive STAT5 activationViral infectionSTAT5 phosphorylationPrecursor cellsSurvival